Zika virus (ZIKV) is an emerging mosquito-borne pathogen (family Flaviviridae, genus Flavivirus), believed to be transmitted to humans by infected Aedes spp. mosquitoes. Recent studies have demonstrated that ZIKV is endemic to Africa and Southeast Asia, causing significant health concern globally. In May 2015, the Pan American Health Organization (PAHO) issued an alert regarding the first confirmed ZIKV infection in Brazil. On Feb. 1, 2016, the World Health Organization (WHO) declared ZIKV a Public Health Emergency of International Concern (PHEIC) regarding a recent cluster of microcephaly cases and other neurological disorders and the possible association of these illnesses with ZIKV infections.
As many as four million people could be infected by the end of 2016. About 1 in 5 people infected with ZIKV become ill (i.e., develop Zika). ZIKV infection is characterized by mild fever (37.8° C.-38.5° C.); arthralgia, notably of small joints of hands and feet; myalgia, headache; retroorbital pain; conjunctivitis; and cutaneous maculopapular rash. ZIKV infection is believed to be asymptomatic or mildly symptomatic in most cases. Thus, Zika can be misdiagnosed during the acute (viremic) phase because of nonspecific influenza-like signs and symptoms. Hemorrhagic signs have not been reported in ZIKV-infected patients. However neurologic complications, including Guillain-Barré syndrome, have been observed. Recent data also show that the Brazilian ZIKV (ZIKVBR) strain infects fetuses and causes birth defects including microcephaly (Nature 534, 267-271 (9 Jun. 2016)).
Diagnosis of Zika fever requires virus isolation and serology, which are time consuming or cross-reactive, and make rapid serologic confirmation difficult. Thus, improved technology for rapid, sensitive detection of Zika is urgently needed.
ZIKV is additionally unique among the flaviviruses in that it is known to be transmissible by men to their sexual partners via infection of semen. ZIKV is found in semen for a longer period of time than in blood, urine, saliva or other tissues samples. Several case reports exist where men transmitted Zika to their sexual partners after returning from an area of active viral transmission (Evidence of Sexual Transmission of Zika Virus. D'Ortenzio E, Matheron S, Yazdanpanah Y. N Engl J Med 2016; 374:2195-2198, Jun. 2, 2016). In these cases, the partner had no travel history in an affected area. At the current time, information regarding the duration of Zika shedding in semen and the infectivity of different viral loads is scant or absent. A recent report from France noted a viral load of 1×108.6 copies/mL in semen of a patient returning from Brazil (Zika virus: high infectious viral load in semen, a new sexually transmitted pathogen? Mansuy, J M, Dutertre, M, Mengelle, C et al. Lancet Infect Dis. 2016; 16: 405).
It is now documented that Zika is retained in semen for over 6 months (Barzon L, et al., Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016. Euro Surveill. 2016; 21(32)). This underscores the need for a semen-based diagnostic assay for Zika. Recent reports separately document the transmission of the virus from an asymptomatic male to their sexual partner (Brooks R B et al., Likely Sexual Transmission of Zika Virus from a Man with No Symptoms of Infection—Maryland, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:915-916; Fréour T et al., Sexual transmission of Zika virus in an entirely asymptomatic couple returning from a Zika epidemic area, France, April 2016. Euro Surveill. 2016; 21(23)). In these cases, the male may not realize they are carriers of the virus in the absence of normal symptoms. Additional review of Zika virus can be found in “Zika virus,” Musso D, Gubler D J. 2016. Clin Microbiol Rev 29:487-524.
One of the barriers to the development of diagnostic tests using sperm is the difficulty in working with this sample type. Thus, an urgent need exists for a highly sensitive and robust assay for Zika detection in semen.